報 告 人

Liang Zhao-Xun (梁照珣)

報告時間

2024年12月16日 19:00-20:10

報告地點(diǎn)

B248視頻會議

報

告

內(nèi)

容

簡

介

報告內(nèi)容簡介：Anthraquinone-fused enediynes are anticancer natural products featuring a DNA-intercalating anthraquinone moiety. Despite recent insights intoanthraquinone-fusedenediyne (AQE) biosynthesis, the enzymatic steps involved inanthraquinone biogenesis remain to be elucidated. Through a combination of invitro and invivo studies, we demonstrated that a two-enzyme system, composed of a flavin adenine dinucleotide (FAD)-dependent monooxygenase (DynE13) and a cofactor-free enzyme (DynA1), catalyzes the final steps of anthraquinone formationby converting δ-thiolactone anthracene to hydroxyanthraquinone. We showed that the three oxygenatoms in the hydroxy anthraquinoneoriginate frommolecular oxygen (O2), with the sulfur atom eliminated as H₂S. We further identified the key catalytic residues of DynE13 and A1 by structural andsite-directed mutagenesis studies. Our data support a catalytic mechanism wherein DynE13 installs two oxygen atoms with concurrent desulfurization and decarboxylation, whereas DynA1 acts as a cofactor-free monooxygenase, installing the final oxygen atom in the hydroxyanthraquinone. These findings establish the indispensable roles of DynE13 and DynA1 in AQE biosynthesis andunveil novel enzymatic strategies for anthraquinone formation.

報告人簡介：Zhao-Xun Liang obtained his bachelor's and master's degrees in organic chemistry from Lanzhou University in China. He did his Ph.D. studies in Chemistry at Northwestern University, where he conducted research under the guidance of Brian Hoffman. He was a postdoctoral fellow with Judith Klinman at the University of California, Berkeley before joining the School of Biological Sciences of Nanyang Technological University (NTU) of Singapore as an assistant professor. He is currently a professor at NTU working in the fields of enzyme discovery and synthetic microbiology.

承辦單位

藥學(xué)院

發(fā)布日期

2024.12.16